Learning Week 10 and 11

Workshop (PHRM3301, PHRM3031)

Adam La Caze

Learning objectives for the week

LW10: Diagnostic tests and screening

  1. Be able to describe and calculate the properties of a test for disease: sensitivity, specificity, positive predictive value, negative predictive value
  2. Be able to assess the usefulness of a diagnostic or screening test
  3. Be able to describe the common sources of bias when assessing a screening test

LW11: How things can go wrong

  1. How can the pharmaceutical industry influence decisions?
  2. How do we treat individuals based on data from populations?
  3. Understanding the ways in which our methods are fallible

Extend activities

LW10

  • Diagnostic tests
    • Covid-19; sensitivity, specificity, positive predictive value, negative predictive value
    • Troponin and acute coronary syndrome
    • Deciding test cut-offs
  • Disease screening
    • Breast cancer screening

LW11

  • Marketing-based medicine (Spielmans and Parry 2010)
  • The subgroup problem
    • Clopidogrel and ticagrelor
  • Why most published research findings are false*

Course and teaching evaluation (PHRM3301)

Written exam

Details (PHRM3301)

  • The written exam is worth 30% of the marks of the course
  • It as an on-campus invigilated exam via Inspera.
  • The exam will be 120 minutes with 10 minutes reading time.
    • 120 marks (1 mark per minute)
    • 80 marks clinical epidemiology (Adam: LW1–4, 10–11)
    • 40 marks statistics (Ian: LW5–9)
  • See the sample exam!

Details (PHRM3031)

  • The written exam is worth 50% of the marks of the course
  • It as an on-campus invigilated exam via Inspera.
  • The exam will be 60 minutes with 10 minutes reading time.
  • See the sample exam!

Diagnostic tests

Covid-19, RAT test properties

A company that has produced a new rapid antigen test to detect Covid-19 needs to demonstrate that it has sufficient sensitivity and specificity to pass regulatory requirements.

They conduct a study comparing the RAT outcomes to a real-time reverse-transcription polymerase chain reaction (rRT-PCR) test.

100 people with symptoms of respiratory tract infection are enrolled, 15 people are identified as Covid-positive via rRT-PCR. Of these 15 people, 14 are identified as Covid-positive according to the RAT. Three people with a negative rRT-PCR test were identified as positive according to the RAT.

Determine the sensitivity and specificity of the RAT test and the prevalence of Covid in this sample.

Condition No condition Total
Test \(+\) 14 3 17
Test \(-\) 1 82 83
Total 15 85 100

\(Sn = \frac{a}{a + c} = 14/15= 93\%\)

\(Sp = \frac{d}{b + d} = 82/85 = 96\%\)

\(P = \frac{a + c}{a + b + c + d} = 15/100 = 15\%\)

Predict what will happen to the positive predictive value and negative predictive value of the test if the prevalence of Covid in the community changes.

Condition No condition Total
Test \(+\) \(a\) \(b\) \(a + b\)
Test \(-\) \(c\) \(d\) \(c + d\)
Total \(a + c\) \(b + d\) \(a + b + c + d\)

Disease screening

Early detection of breast cancer by mammography

Review the information provided by Harding Centre for Risk Literacy (below).

  1. How would you describe this data to a 50 year old woman considering screening?
  2. What are the uncertainties in the data? (What are the challenges in obtaining reliable data?)
  3. Why aren’t incidence rates and 5-year survival reported?

How things can go wrong

Marketing-based medicine: Problems and replies

  1. Describe ways that the pharmaceutical industry can undermine evidence-based medicine

  2. What tools are available to identify and/or mitigate these attempts?

The subgroup problem

Explain the subgroup problem.

Semaglutide and cardiovascular outcomes (Lincoff et al. 2023)

Participants People over 45 with BMI > 27 and established cardiocascular disease and NOT a diagnosis of diabetes
Intervention Semaglutide sc once-weekly (escalating dose to 2.4 mg)
Comparator Placebo
Outcome Composite: Death from cardiovascular disease, nonfatal MI, nonfatal stroke

The trial included 17 604 participants and the sample was ~ 72% male and 84% white

Ioannidis’ Why most published research is false*

Explain the following table:

References

Lincoff, A. Michael, Kirstine Brown-Frandsen, Helen M. Colhoun, John Deanfield, Scott S. Emerson, Sille Esbjerg, Søren Hardt-Lindberg, et al. 2023. “Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes.” New England Journal of Medicine 389 (24): 2221–32. https://doi.org/10.1056/NEJMoa2307563.
Spielmans, Glen I, and Peter I Parry. 2010. “From Evidence-Based Medicine to Marketing-Based Medicine: Evidence from Internal Industry Documents.” Journal of Bioethical Inquiry, January, 1–17. https://doi.org/10.1007/s11673-010-9208-8.